1. Field of the Invention
The present invention relates to a portable radiofrequency (RF) hyperthermia device having flexible applicator treatment electrodes for electric field capacitive coupled energy transfer, the device being useful for increasing the delivery of a systemically delivered drug at a localised target site. The portable RF device is suitable for use by a patient in their own home and the flexible applicator is a flexible, porous, light and easy to manipulate treatment electrode. The inventive device requires no specialist operator to ensure correct usage.
2. Description of the Relevant Art
Heating is widely applied in a many areas of medicine and also used for cosmetic treatments. For example radiofrequency/microwave hyperthermia devices can be used to force energy absorption in tissue to cause damage to unwanted structures and/or increase the temperature of a targeted area above the normal body temperature. One use of hyperthermia devices is the treatment of cancer. Another use for hyperthermia devices is to increase temperature and blood circulation for cosmetic (fat-burning, lipid-distortion, shape-correction, etc), dermatological and pain relief treatments.
A usual therapy for many diseases for curative and/or palliative purposes is the administration of a drug. A drug can be administered by a number of possible routes, for example, orally and/or intravenously and/or injected into muscles or arteries. These modes of drug delivery result in systemic exposure to the drug. However, the disease is often mainly localized to a specific area, such as a particular organ (liver, lung, kidney, prostate, breast, brain, spleen, stomach, oesophagus, colon, pancreas, etc.). Therefore the maximum exposure to the drug is required only, or mostly, at a localised target site. A common problem of drugs that are required at a local target but are systemically delivered is their systemic actions. The negative consequences are not trivial:                unwanted side effects occur often requiring further treatment to ameliorate the side effects,        the administration of the drug is non-selective and a lower amount of the drug reaches the target site than intended,        a higher dose of drug must be administered than is required at the target site to ensure delivery of a sufficient drug concentration at the target site.        
U.S. Pat. No. 6,330,479 is a state of the art document disclosing a hyperthermia device which uses microwaves. The basic idea of the device described in U.S. Pat. No. 6,330,479 is far from the present disclosure. U.S. Pat. No. 6,330,479 discloses a portable belt or garment for inducing hyperthermia. It is a surface heating, when the microwave has a role to keep the liquid warm (keep on definite temperature) and so heat up the skin where the belt/garment is fixed. The similarity that it fits well to different body contours is very formal, because the heating mechanism does not fit at all. The applicator (belt/garment) in U.S. Pat. No. 6,330,479 has a contact heating making the blood-perfusion high in the surface area, and remaining ineffective in the deep target. The heat is not generated in depths and consequently the effect of the present disclosure isn't realized. If (by long-time application) the heating could reach deeper volumes it does not promote selective drug delivery, because of the above. In principle, not targeted layers have a higher temperature so they are targeted by the medicaments of the ionizing radiation much more than the selected tissue itself. The contact hot-spots (and their elimination by distances) is also far from the present disclosure and solution. The present deep heating does not heat up the surface. At the contrary, it is taken care on its proper cooling by a porous structure or even by extra air or fluid cooling. The extra cooling process in U.S. Pat. No. 6,330,479 is a large, complex and complicated solution. The metalized porous textile or other suitable materials of the present disclosure such as conductively coated flexible carrier, coated flexible material, conductive metallic net or a conductive metallic network can be used for manufacturing of at least one conductive metal electrode material. Such metallic nets or metallic networks do preferably not comprise any backbone such as a polymeric network structure. The metallic net or network is preferably a woven structure of metallic fibers having very similar properties as the coated flexible material such as a coated textile. Such metalized porous textile or other suitable materials automatically solve the heating problem without additional technical efforts. Temperature measurement isn't necessary either in the present disclosure (but as an additional option it could be done on the surface). The temperature control is simply the patient's sensing. It isn't intended to heat up the surface higher than tolerable. For the wanted physiological effect not more than 42° C. are needed locally. This is requested for the targeted volume. Higher temperature could cause an opposite effect; it could block the blood-perfusion in the capillaries, mainly in solid tumors. The surface heating (according to U.S. Pat. No. 6,330,479) faces the problem of a temperature gradient, which requires the comparatively highest temperature at the surface to penetrate deeper. The disclosed portable RF hyperthermia device does the opposite. The surface could be kept on body temperature and at the same time the targeted volume could be heated up by penetration of the RF-current. The device constructed according to U.S. Pat. No. 6,330,479 appears rather complicated to handle as well as uncomfortable to wear for the patient and delimits considerably his/her mobility. The aim of improved drug availability in the heated tissue is not addressed at all in U.S. Pat. No. 6,330,479 and it cannot be achieved because the increased blood perfusion is limited to the surface area.
U.S. Pat. No. 6,330,469 discloses a completely a different apparatus and a completely different idea of application than the present disclosure. It does not provide the advantages of selective drug targeting (except at the surface area), it compromises the patient's mobility and it can not heat in deeper layers. The present disclosure does not require a cooling system and an easy handling will provide a positive feedback in the long run.
WO 00/51513 A is another state-of-the-art document disclosing an invasive energy delivering system, dedicated to a special need of vascularization. It is not drug- or radio-targeting and it does not target capillaries. This is a highly specialized device in heart physiology (cardiology). In contrast, the present disclosure is a non-invasive heat-delivery device for any body part, it is promoting the revascularization of capillaries, it can be combined with systemically administered drugs (even in oral, inhalatory, topical, parenteral, injection or other systemic drug delivery). The drugs can be effectively reoriented and redistributed to the desired (targeted) tissue especially due to increased blood-perfusion. WO 00/51513 A clearly reveals an invasive method. This device is only suitable for the use in hospital. The patient is under full anaesthesia or at least highly sedated and immobilized. The present disclosure allows the patient a comparatively wide range of moving around freely, no further medication (palliative or other safety medication) is necessary for its application. The device from WO 00/51513 A uses water cooling channels inside the catheter for keeping the surface temperature in a safe range. In this aspect WO 00/51513 A uses the same solution as in U.S. Pat. No. 6,330,469: It has conductive heat-diffusion, it provides the highest temperature at the outermost surface of the application area and the heat flows according to the temperature gradient. Both U.S. Pat. No. 6,330,469 and WO 00/51513 A are typical thermal conductivity systems showing all the disadvantages of this approach. U.S. Pat. No. 6,330,469 and WO 00/51513 A are much more similar to each other than to the present disclosure.